PROJECT SUMMARY/ABSTRACT All motor output is generated by motoneurons and consequently their firing patterns contain detailed information about the structure of motor commands. Remarkably, this information is accessible in humans, because motoneuron spikes are 1 to 1 with those of their muscle fibers. Our overall concept is that motoneuronal firing patterns vary systematically across the muscles of the human body and that this variation reflects fundamental connections between the synaptic organization of motor commands, the structure of the musculoskeletal system and the diversity of motor tasks. To understand these connections, our overall goal is to create a detailed ?motor output map? of the human body, using newly developed array electrodes. The array electrodes are placed on the skin and are capable of measuring the firing patterns of up to 30 motor units simultaneously in the underlying muscle. We plan further technical development of these arrays to expand the range of motor tasks they can be used for. The human motor output map will be created from the analysis of firing patterns of populations of motor units in muscles throughout the body for matched motor tasks. We will interpret the resulting map in light of our recent advances in understanding of how firing patterns of motoneurons are determined by the organization of their synaptic inputs. The effects of excitatory and inhibitory inputs on firing patterns are fundamental for generating firing patterns, but neuromodulatory inputs from the brainstem are equally if not more important. These neuromodulatory inputs release serotonin and norepinephrine, which have a profound influence on the intrinsic excitability of motoneurons and thus control how motoneurons process their excitatory and inhibitory inputs. In Aim 1, we create a basic version of the human motor output map by asking subjects to generate slow linear increases and decreases in torque for more than 20 muscles across the body. The protocol is kept exactly the same across muscles to allow comparisons of the resulting firing patterns. Our primary hypothesis is that muscles involved in stabilization of the body, such as proximal muscles, will generate motor unit firing patterns consistent with high levels of neuromodulatory drive, while muscles involved more in precision tasks will generate patterns consistent with low levels of neuromodulation. These experiments are essentially function anatomy, the proximal-distal variations in firing patterns probably arise from differences in the anatomical projections of synaptic inputs to motor pools. In Aim 2, we assess whether there are task dependent changes in firing patterns, such as increases in neuromodulation drive with increased effort and increases in sensory inhibition with movement. Taken together, these experiments will define the fundamental structure of motor output for the human musculoskeletal structure and provide a quantitative basis for understanding the distortions that occur in disease states like spinal cord injury.